OBJECTIVES: In a prospective population-based study covering a German region with 200.000 inhabitants, the incidence of severe hypoglycaemia (SH) and clinical characteristics of the corresponding patients were longitudinally compared over two four-year periods between 1997-2000 versus 2007-2010. METHODS: Blood glucose testing was systematically performed in every emergency patient irrespective of the presenting condition, either already prehospitally at the scene of the emergency or immediately after the arrival at the emergency department, respectively. SH was defined as a symptomatic event requiring treatment with intravenous glucose and was confirmed by a blood glucose measurement of <50 mg/dl. RESULTS: Warranting identical methodological conditions, our study revealed a drastic increase of 87.5% in the frequency of SH (495 events in 2007-2010 versus 264 events in 1997-2000). There was no change in the distribution of SH within the different types of diabetes. The incidence of SH between 1997-2000 versus 2007-2010 increased considerably from 11.5 to 22.7 in patients withT1DM and from 18.5 to 32.5 in those with T2DM. We observed a clear shift towards intensification of antihyperglycemic therapy as indicated by lower HbA1c values in increasingly multimorbid subjects. Especially hypoglycemic subjects with T2DM were characterized by a geriatric and multimorbid state (mean age >75 years) receiving additional comedication of 3.3 (1997-2000) versus 7.7 drugs (2007-2010) and suffering from 3.6 versus 4.4 concomitant diseases with an increase in renal insufficiency from 54% to 76% (respective p-values <0.001). CONCLUSIONS: The nationwide growing incidence of diabetes might have substantially contributed to the considerable increase of SH between 2007-2010. Furthermore, the increase of SH correlated with the shift towards more stringent goals for metabolic control by official German guidelines (currently HbA1c<6.5%) and the implementation of Disease Management Programs for Diabetes in 2003 leading to intensification of antihyperglycemic therapy and thus increasing the risk for SH.